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Biomedical subjects

M Audran

Publications and source records attributed to M Audran.

At least 37 records · Page 2Linked to original sources
PubMed2000

Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis.

Some studies have indicated that the risk of fragility fractures in men increases as bone mineral levels decrease, but there is an overlap in the bone mineral density (BMD) measurements between patients with or without fractures. Furthermore, it has been suggested that the biomechanical competence of trabecular bone is dependent not only on the absolute amount of bone present but also on the trabecular microarchitecture. In the present study, 108 men (mean age 52.1 years) with lumbar osteopenia (T score < -2.5) were recruited to examine the relationships between BMD, architectural changes in trabecular bone, and the presence of vertebral fractures. Lumbar BMD was assessed from L2 to L4 in the anteroposterior view with dual-energy X-ray absorptiometry. At the upper left femur, hip BMD was measured at the transcervical site. Spinal X-ray films were analyzed independently by two trained investigators, and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle, or posterior vertebral height. Transiliac bone biopsy specimens were obtained for all patients. Histomorphometric studies were performed on an image analyzer, and the following parameters were determined: trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), number (Tb.N), and separation (Tb.Sp), interconnectivity index (ICI), characterization of the trabecular network (node count and strut analysis), and star volume of the marrow spaces. Spinal radiographs evidenced at least one vertebral crush fracture in 62 patients (group II) and none in 46 patients (group I). After adjusting for age, body mass index, and BMD, there were no significant differences between the two groups in BV/TV, Tb.Th, or star volume. In contrast, the mean values of ICI, free end-to-free end struts (FF/TSL), and Tb.Sp were significantly higher, whereas Tb.N and node-to-node struts (NN/TSL) were lower in patients with at least one vertebral fracture. Logistic regression analysis showed that only ICI, FF/TSL, NN/TSL, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of 1 SD ranged from 1.7 (1.0-3.2) for NN/TSL to 3.2 (1.1-10.1) for ICI. Patients with at least three vertebral fractures (n = 23) were categorized as "multiple fractures." The results of logistic regression showed that spine BMD, BV/TV, and all architectural parameters were significant predictors of multiple vertebral fractures: odds ratios for an alteration of 1 SD ranged from 2.2 (1.1-4.6) for star volume to 3.7 (1.4-9.7) for ICI. These results strongly suggest that bone trabecular microarchitecture is a major and independent determinant of vertebral fractures in middle-aged men with osteopenia.

Absorptiometry, Photon↗
PubMed2000

[Osteoporosis in males].

A shorter life expectancy, a higher peak bone mass and the absence of distinct menopause equivalent explain the lower incidence of osteoporotic fractures in men. In contrast to women, osteoporosis in younger men is in most cases secondary. Causes such as prolonged glucocorticoid therapy, ethanol abuse, hypogonadism and gastrointestinal disorders are now well recognized. The impact of cigarette smoking, low calcium intake, vitamin D deficiency, hypercalciuria and thyrotoxicosis is more controversial but seems to constitute real risk factors for bone loss. Furthermore increased propensity to fall also plays a major role in fracture risk, particularly in alcoholic patients and in elderly men with neurologic disorders.

Age Distribution↗
PubMed1999

Assay method for the perfluorooctyl bromide (perflubron) in rat blood by gas chromatography-mass spectrometry.

This paper describes a GC-MS method (SIM mode) for the analysis of perfluorooctyl bromide (perflubron, I) in rat blood. The chromatographic separation was performed by injection in the split mode using a CP-select 624 CB capillary column. Following destruction of the emulsion by addition of ethanol, the analytical procedure involves a liquid-liquid extraction with 1,1,2-trichlorotrifluoroethane. The bis(F-butyl)ethene (II) was used as internal standard. Observed retention times were 3.22 min for I and 2.32 min for II. Two calibration curves were used; linear detection responses were obtained for concentrations ranging from 0.009 to 0.9 mg/ml and from 0.9 to 13.5 mg/ml. The extraction efficiency averaged 50% for I and 93% for II. Precision ranged from 0.7 to 14%, and accuracy was between 91 and 109%. The limit of quantification was 9 microg/ml. The method validation results indicate that the performance characteristics of the method fulfilled the requirements for assay method for use in pharmacokinetic studies.

Animals↗
PubMed1999

High-performance liquid chromatographic method for the determination of atracurium and laudanosine in human plasma. Application to pharmacokinetics.

A high-performance liquid chromatographic method coupled with fluorimetric detection has been developed for the determination of atracurium and its major metabolite, laudanosine, in human plasma. The detection is performed at 240 nm for excitation and 320 nm for emission. Verapamil was used as the internal standard. The proposed technique, involving the direct precipitation of plasma proteins is reproducible, selective and sensitive. Linear detector responses were observed for the calibration curve standards in the range of 40 to 2000 ng/ml. Precision, expressed as C.V., was in the range 1 to 14%. The limit of quantification for both atracurium and laudanosine was 40 ng/ml. The method has been validated and stability tests under various conditions have been performed. This method has been used to determine the pharmacokinetic profile of atracurium and laudanosine in patients with acute respiratory distress syndrome.

Atracurium↗
PubMed1999

[Prolonged suppressive L-thyroxine therapy. Longitudinal study of the effect of LT4 on bone mineral density and bone metabolism markers in 71 patients].

OBJECTIVES: A prospective longitudinal study was conducted to investigate the influence of prolonged suppressive L-thyroxin therapy on bone density and biochemical markers of bone remodeling. PATIENTS AND METHODS: Seventy-one patients (including 28 menopaused women) taking long-term L-T4 for thyroid carcinoma were divided into 3 groups according to their TSH level: low (TSH < 0.04 mlU/l), moderate (0.04 TSH < or = 0.10 mlU/l) and high (TSH > 0.10 mlU/l). Bone density was measured in lumbar vertebrae annually for a mean 4.5 years. Bone metabolism markers were measured over a 4 year period. Bone density measurements of the femur were also obtained for 2 years in 16 menopaused women. RESULTS: Lumbar bone density did not decline whatever the TSH level or the duration of L-T4 treatment. Likewise for menopaused women without substitution estroprogesterone therapy. Over the 4 years, biochemical markers of bone formation, including bone alkaline phosphatases and osteocalcin, or of bone resorption, including urinary hydroxyprolin, did not vary. In addition, in menopaused women, femoral bone density was not significantly lowered over the 2 years follow-up. No lumbar or femoral osteopenia was observed in these patients taking L-thyroxin, even for those with complete TSH blockade. Biochemical markers did not demonstrate a significant acceleration of bone turnover during prolonged administration of L-T4 at suppressive levels.

Adult↗
PubMed1999

Bone mineral density and vertebral fractures in men.

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score < -1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward's triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3-2.8) for spine BMD to 2.3 (1.5-3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1-2.5) for spine BMD to 2.6 (1.7-4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score < -2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score < -2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia.

Absorptiometry, Photon↗
PubMed1999

[Bone mineral density in patients with cystic fibrosis by dual-energy X-ray absorptiometry].

BACKGROUND: The aim of this study was to assess the bone mineral density of cystic fibrosis patients. PATIENTS AND METHODS: We have retrospectively studied 45 patients with cystic fibrosis, 22 females and 23 males, aged between six and 27 years (mean 13 +/- 5.5 years). Nutritional status, Shwachman score, pulmonary function, serum calcium and 25-hydroxyvitamin D levels and lumbar bone mineral density by dual energy X-ray absorptiometry were assessed. RESULTS: The average height of the patients was 97 +/- 4% (range: 86-106) and body mass index 93 +/- 10% (range 77-114) of the normal values of age. The average Shwachman score was 80 +/- 11/100 (range: 47-96). The forced expiratory volume in 1s was 80 +/- 29% (21-128) and the vital capacity 85 +/- 21% (range: 40-122) of the predicted values. The serum levels of calcium and 25-hydroxyvitamin D were lower than normal values in six cases and one case respectively. Thirty-eight patients had a mean lumbar spine bone mineral Z-score which was -1.35 +/- 1.2 DS and 84.7 +/- 13.5% of the normal values. It was correlated with the height, the body mass index, the Shwachman score, the FEV 1 and the vital capacity. CONCLUSION: Decreased bone density is frequent among cystic fibrosis subjects. It shows a lack of control of the illness. It remains unknown with usual investigation; the dual X-ray absorptiometry should, each time it is possible, take part of investigations in those patients.

Absorptiometry, Photon↗
PubMed1999

Effects of erythropoietin administration in training athletes and possible indirect detection in doping control.

PURPOSE: This study investigated the effects of repeated subcutaneous injection of rHuEpo (50 IU x kg(-1)) in athletes and proposes a method based on the measurement in blood samples of the sTfR/serum protein ratio to determine if the observed values of this marker are related to rHuEpo abuse. METHODS: Serum erythropoietin concentrations, and hematological and biochemical parameters were evaluated, during treatment and for 25 d posttreatment in nine training athletes. Moreover, the effect of rHuEpo administrations on the maximum oxygen uptake (VO2max) and ventilatory threshold (VT) of these athletes was also studied. Threshold values for sTfr and the sTfr/serum protein ratio were determined from 233 subjects (185 athletes, 15 athletes training at moderately high altitude, and 33 subjects living at >3000 m). RESULTS: Significant changes in reticulocytes, hemoglobin (Hb) concentration, hematocrit (Hct), sTfr, and sTfr/serum proteins were observed during and after rHuEpo treatment. The maximal heart rate of 177 beats x min(-1) at the beginning of the study was significantly higher than the value of 168 beats x min(-1) after 26 d of rHuEpo administration. Compared with the values measured at baseline, the VT measured after rHuEpo administration occurred at a statistically significant high level of oxygen uptake. CONCLUSIONS: When oxygen uptake measured at the VT was expressed as a percentage of V02 max, the values obtained were also significantly higher. The increased values of Tfr and sTfr/serum proteins, respectively, above 10 microg x mL(-1) and 153, indicated the probable intake of rHuEpo.

Adult↗
PubMed1999

[Histomorphometric measurement of the architecture of the trabecular bone in osteoporosis: comparative study of several methods].

Osteoporosis is now defined as a disease characterized by a decreased bone mass associated with micro-architectural modification of trabecular bone leading to an increased fragility and to bone fractures. Various histomorphometric methods have been described to measure bone architecture on histological sections. However, not all of methods are strictly equivalent and some of them appear able to detect differences earlier in the course of the disease. We have compared 8 histomorphometric methods known to characterize the architecture of trabecular bone in 55 male osteoporotic patients. Measurements were done on transiliac bone biopsies: Trabecular number, thickness and separation (Tb.N, Tb.Th, Tb.Sp); Trabecular Bone Pattern Factor (TBPf); Euler-Poincaré's number (E); Interconnectivity Index (ICI); strut analysis of the trabecular network with the ratio of nodes/free-end (N/F); star volume of the bone marrow (Vm) and trabeculae (Vtrab) and the Kolmogorov fractal dimension of the trabecular boundaries (D). Relationships between the various architectural parameters were studied by hierarchical cluster analysis. Linear, hyperbolic and exponential correlations were found between trabecular bone volume (BV/TV) and architectural parameters. Cluster analysis demonstrates the link between these architectural parameters. ICI, E and TBPf which reflect the amount of open/closed marrow cavities clustered together and appeared related to Tb.Sp, which are indicators of the mean size of marrow cavities. Tb.Th, Vm and N/F flocked together as they reflect the trabecular size. Tb.N and D segregated together and seemed to best describe the trabecular network complexity. These histomorphometric techniques are correlated but correlations may be linear or non linear. Several histomorphometric techniques need to be used in parallel to appreciate the pathophysiological mechanisms of osteoporotic states.

Bone and Bones↗
PubMed1999

[Trabecular bone microarchitecture and male osteoporosis].

In men the risk of fragility fractures increases as bone mineral density (BMD) declines but the mechanical strength of vertebrae is also dependent on the trabecular architecture. We have examined the relationships between architectural changes of trabecular bone and vertebral crush fractures in 44 male patients with osteoporosis (bone mineral density more than 2.5 SD below the young adult value). Spine radiographs, hip and lumbar spine BMD and transiliac bone biopsies were obtained for all subjects. Histomorphometric study was done on an image analyzer and the following parameters were determined: trabecular bone volume (BV/TV), trabecular thickness (Tb.Th) and number (Tb.N), Trabecular Bone Pattern factor (TBPf), Inter Connectivity Index (ICI), characterization of the trabecular network (Node count and Strut analysis) and Star volume of the marrow space. Eleven male patients, who were referred to our unit for the diagnosis a monoclonal gammopathy of undetermined significance, were selected as controls. The mean values of Tb.Th, Tb.N and Node count were found lower while TBPf, ICI and Star Volume were significantly higher in men with osteoporosis. Exponential regressions were found to best describe the relationships between BV/TV and the architectural parameters: TBPf (r = 0.94 p = 0.01), ICI (r = 0.63 p = 0.001), Star volume (r = 0.79 p = 0.001). There were no significant differences in age, vertebral and hip BMD, BV/TV and Tb.Th between patients with or without fracture. In contrast, in patients with at least one vertebral fracture, ICI and TBPf were significantly higher while Nodecount was lower. Our data suggest that an altered trabecular bone architecture is a major determinant of osteoporotic fractures in men.

Adult↗
PubMed1998

Reversed-phase high-performance liquid chromatographic determination of enoxacin and 4-oxo-enoxacin in human plasma and prostatic tissue. Application to a pharmacokinetic study.

A simple high-performance liquid chromatographic method has been developed for the simultaneous determination of enoxacin and 4-oxo-enoxacin in plasma and prostatic tissue. The work-up procedure involves a liquid-liquid extraction step followed by isocratic chromatography on a reversed-phase analytical column, with ultraviolet absorbance detection (lambda = 340 nm). Using a mobile phase of 20.9% (v/v) acetonitrile buffer (pH 2.1), adequate retention time and separation among the analytes has been obtained using tetrabutylammonium hydroxide included in the eluent. Retention times are 5.2 min for enoxacin, 6.8 min for pefloxacin and 12 min for 4-oxo-enoxacin. For plasma and prostatic tissue, the precision of the assay was below 9%. The percent recovery from the nominal values for accuracy ranged from 94 to 108%. The limits of quantitation were 20 ng/ml for plasma and 50 ng/g for tissue (precision < 18%). The detection limits were 10 ng/ml and 25 ng/g, respectively. The calibration curves were linear from 20 to 1000 ng/ml for plasma and from 50 to 2500 ng/g for tissue. In plasma, the extraction recoveries averaged 52% for enoxacin and 63% for 4-oxo-enoxacin. In prostatic tissue, they were 57 and 76% for the two analytes, respectively. This method has been employed for the determination of enoxacin and 4-oxo-enoxacin in plasma and prostatic tissue samples from patients following repeated oral administration of enoxacin (400 mg twice a day for four days).

Adenoma↗
PubMed1998

Increased nucleolar organizer regions in osteoclast nuclei of Paget's bone disease.

The etiology of Paget's disease of bone is still unknown but several studies have reported a viral origin. At the electron microscopic level, characteristic nuclear and cytoplasmic inclusions have been found and mimic paramyxoviral nucleocapsids in osteoclasts (Oc). Sarcomatous degeneration is observed in 2% of pagetic patients. Nuclear organizer regions are parts of the nucleolus involved in the synthesis of ribosomes, and they contain nonhistone proteins that can be silver stained (AgNORs) on the interphasic nuclei. AgNOR number is known to correlate with the proliferative activity of the cell populations, whether normal or malignant. Cancer cells have an increased demand for (robosomal) rRNA and correlations have been found between AgNORs and proliferative antigens. We have adapted the AgNOR staining method to undecalcified bone biopsies at the light and TEM levels. Bone sections from 10 pagetic patients (without a previous bisphosphonate treatment) were stained for AgNORs. 10 patients having metabolic bone diseases associated with an increased Oc number (i.e., primary and secondary hyperparathyroidism) were used as controls. AgNORs appeared as black dots within the nucleoli of Oc nuclei and were easily numbered. A maximum of two or three dots could be seen in Oc nuclei from control subjects. In pagetic Oc, AgNOR number was greatly increased (6.80 +/- 2.57 dots vs. 2.12 +/- 1.07 in controls). TEM study also showed AgNOR in the nucleoli of pagetic patients' Oc. The viral inclusions within the nuclei appeared faintly stained and could not be confused with AgNORs. The large number of AgNORs in the nuclei of pagetic Oc reflects the need for a greater abundance of ribosomes. With the pagetic Oc being highly active, the cytoplasmic synthesis of proteins is maximized (probably hydrolases involved in the matrix breakdown). An increase in AgNORs does not reflect the proliferative activity of the cell because Oc are made by the fusion of precursors. It is postulated that: (a) other mRNAs (of viral/oncogene origin) could be actively transcribed in pagetic patients and require more numerous ribosomes; or (b) a viral genome/oncogene promotes alteration of the nuclear/nucleolar mechanism.

Cell Nucleus↗
PubMed1998

Different patterns of extension and recurrence in algodystrophy.

A true recurrence at exactly the same site is quite unusual in algodystrophy. Local or regional extension is possible. The bone scan is an easy way to demonstrate that the areas successively affected are not the same. An apparent local recurrence could in fact be a microscopic compression fracture of trabecular bone or cortical fractures or part of a factitious disorder.

Adult↗
PubMed1998

Further vascular, bone and autonomic investigations in algodystrophy.

Direct clinical observation is the most common means of diagnosing algodystrophy. Further investigations may be helpful to rule out other pathological conditions, such as occult or stress fractures or avascular osteonecrosis and to obtain a better understanding of algodystrophy. Transient vascular hyperpermeability in the affected part is well demonstrated by the clinical findings, the MRI signs, and the three-bone scan features. 99m Technectium EHDP bone scan provides an evaluation of the vascular abnormalities and of the osteoblastic activity. Dermal microcirculation and its reactions to sympathetic stimuli are investigated by laser doppler fluximetry and videophotometric capillaroscopy. Perhaps the sweat test does unveil what might be specific about algodystrophy. The amount of bone loss in algodystrophy in a few weeks or months is what might be expected over 10 years during the natural history of uncomplicated osteoporosis. An initial fracture is undoubtedly an initiating event in the appearance of algodystrophy, but patients suffering from algodystrophy may still have significant osteoporosis for a long period and hence be at risk for fracture. Densitometry could be an aid to the diagnosis and probably to monitoring treatment as well. The local colonization of fibroblasts following the transient stage of hyperpermeability must be kept in mind to explain the results of joint, bone, muscles or neurological investigations in late algodystrophy.

Absorptiometry, Photon↗